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Finasterida- Mitos e Verdades - Dr Conrado Alvarenga - Aula ministrada na Sociedade Brasileira de Dermatologia 2014

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Mitos e verdades a respeito da finasterida e seus efeitos sobre fertilidade e sexualidade masculina. Dr Conrado Alvarenga

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Finasterida- Mitos e Verdades - Dr Conrado Alvarenga - Aula ministrada na Sociedade Brasileira de Dermatologia 2014

  1. 1. Finasteride x Male Fertility Testosterone and Sperm Conrado Alvarenga Hospital das Clinicas da FMUSP Responsável Andrologia Clinica Vida bem Vinda - SP
  2. 2. Queda da fertilidade masculina pelo mundo • The research = 26,600 men showed a "significant and continuous" 32.2% decrease in sperm concentration over 17 years. • Sperm per millilitre of semen fell at about 2% a year between 1989 and 2005. • In French men with an average age of 35, sperm count reduced = 73.6 million/ml to 49.9 m/ml.
  3. 3. Queda da fertilidade masculina pelo mundo Dr Le Moal said: "Impairments in the quality of human gametes can be considered as critical biomarkers of effects for environmental stresses, including endocrine disrupters
  4. 4. Queda da fertilidade masculina pelo mundo Dr Le Moal: 1 em cada 5 jovens europeus tem atualmente concentração seminal abaixo ref OMS 2010 – 20% 40% deles não alcançará 40.000.000/ml – cut-off relacionado ao tempo para gestação espontânea
  5. 5. Queda dos níveis de testosterona e androgênios OMS 2012 OBESIDADE CONSUMO DE DROGAS RECREATIVAS SEDENTARISMO MENOR EXPOSICAO AO SOL DISRUPTORES ENDOCRINOS Estudos com nível sócio-econômico Mercado de low – T - EUA 700 PARA 5 BI EM 5 ANOS
  6. 6. METAS  Literatura de qualidade com pelo menos uma revisão sistemática de estudos bem desenhados, randomizados e controlados - estudos puramente dermatológicos ou andrológicos  Entender efeitos da finasterida na espermatogênese e no eixo hormonal masculino  Espermograma e Frag DNA sêmen - pré  Termos de consentimentos  RECOMENDAÇOES E FUTURO
  7. 7. Finasteride is a specific and competitive inhibitor of 5-α-reductase enzyme Type 2, inhibiting the conversion of testosterone to dihydrotestosterone (DHT) A DHT é cerca de 30 vezes mais potente que a testosterona devido à sua afinidade aumentada pelo receptor de andrógenos Aprovada pelo FDA 1997 PARAAlopecia
  8. 8. Concentração de receptores androgênicos na papila é maior
  9. 9. Millions of men have taken or are taking finasteride Early studies did not show significant influence of finasteride on semen parameters Overstreet JW, Fuh VL, Gould J, Howards SS, Lieber MM, Hellstrom W, et al. Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men. J Urol 1999;162:1295–300 whereas some recent observations have suggested that in sub-fertile patients, the effects of the drug might be amplified Glina S, Neves PA, Saade R, Netto NR Jr, Soares JB, Galuppo AG. Finasteride- associated male infertility. Rev Hosp Clin Fac Med Sao Paulo 2004;59:203–5. Liu KE, Binsaleh S, Lo KC, Jarvi K. Propecia-induced spermatogenic failure: a report of two cases. Fertil Steril 2008;90:849.e17–9.Tu HY, Zini A. Finasteride-induced secondary infertility associated with sperm DNA damage. Fertil Steril 2011;95:2125.e13–4.
  10. 10. Eur J Dermatol. 2002 Jan-Feb Long-term (5-year) multinational experience with finasteride 1 mg in the treatment of men with androgenetic alopecia 1,553 men - randomized to receive finasteride 1 mg/day or placebo, and 1,215 men continued in up to four 1-year, placebo-controlled extension studies. Treatment with finasteride led to durable improvements in scalp hair over five years (p 3/4 0.001 versus placebo, all endpoints), while treatment with placebo led to progressive hair loss. Well tolerated and no new safety concerns were identified during long-term use
  11. 11. Dermatology. 2004;209(2):117-25. An open, randomized, comparative study of oral finasteride and 5% topical minoxidil in male androgenetic alopecia CONCLUSION: In this comparative study of systemic finasteride and topical minoxidil, it was concluded that both drugs were effective and safe in the treatment of mild to severe AGA, although oral finasteride treatment was more effective (p < 0.05). Adverse events were not considered important either, and these side effects disappeared as soon as the treatment was stopped. NAO TINHA GRUPO CONTROLE
  12. 12. Finasteride-associated male infertility. Rev Hosp Clin Fac Med Sao Paulo. 2004 Aug; 59 (4):203-5 3 cases of young patients who had very poor seminal quality during finasteride treatment (1 mg/day), and their seminal quality greatly improved after cessation. 2 presented with a left varicocele and the other was obese. We hypothesize that finasteride may not dramatically change the spermatogenesis process in healthy men, but in patients with conditions related to infertility, an amplification of the negative influence of finasteride could occur.
  13. 13. A AZOSPERMIA COM USO DE 1MG/ DIA - APOS CESSAR 4,4 MILHOES/ML B OLIGOSPERMIA COM USO DE 1MG/DIA – APOS CESSAR 18,7 MILHOES/ML 2005
  14. 14. 270 homens 14 – 58 anos com alopécia androgênica – 1mg/dia – t0, 6 meses e 1 ano Hormônios Pré Divididos em dois grupos de ( < = 26 anos e > 26 anos ) No grupo abaixo de 26 anos – Niveis mais altos de 5 alpha-DHT - queda de 50% níveis apos 12 meses ESTUDOS DERMATOLOGICOS SEM TT E ESPG PRE E POS Estudo puramente dermatológico
  15. 15. 2010 We examined 12 men with premature balding Hipótese de DHT envolvida no metabolismo da gordura visceral Após 12 meses de uso 1mg/dia Melhora nos níveis de Hemoglobina Glicada e Resistência Insulínica 12 homens ????????????
  16. 16. 2011 x Twelve studies - (n:3927) Moderate-quality evidence suggested an increase in erectile dysfunction (RR, 2.22) and a possible increase in the risk of any sexual disturbances (RR, 1.39) After cessation of finasteride, sperm concentration was up to more than 10 × 10(6)/mL 16 weeks after stopping finasteride.
  17. 17. Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship.
  18. 18. 1,39 2,22 ASPECTOS SEXUAIS
  19. 19. Global photographic assessment of men aged 18 to 60 years with male pattern hair loss receiving finasteride 1 mg or placebo Duke University Medical Center J Am Acad Dermatol. 2012 Multicenter, double-blind studies randomized patients with vertex hair loss (men aged 18-41 and 41-60 years) to finasteride (1 mg/d) or placebo. A slightly higher incidence of drug-related sexual adverse experiences was reported in the finasteride group than in the placebo group, irrespective of age. x
  20. 20. 2013 The mechanism of the adverse effects of finasteride on male fertility is poorly understood The epididymis plays a critical role in the maturation of sperm and the development of the sperm’s ability to fertilize. Abnormalities of epididymal function could lead directly to infertility.
  21. 21. Danger Routine sperm tests (count, motility, morphology, and leukocyte count) would typically not identify men with altered sperm maturation or fertility potential
  22. 22. ESTUDO PURAMENTE ANDROLOGICO CASE REPORT IFDNA DURANTE USO > 30% 3 MESES SEM 21,2 % APOS 6 MESES 16,5%
  23. 23. Estudo ideal - fusão Duplo Cego - randomizado com placebo – Prospectivo Ajustado para IMC, Hábitos, Maconha......... Com ESPERMOGRAMA PRE COM IFDNA Com ESPERMOGRAMA COM 90 DIAS, 6 MESES E 1 ANO Com Perfil Hormonal Pré e Pós Com Questionário Medicina Sexual ISSM 2014
  24. 24. Já os éxons são as partes “efetivamente” responsáveis pela codificação de proteínas. Durante a transcrição do DNA, os íntrons são removidos por splicing, editando assim o RNA mensageiro, para a posterior produção de proteínas.
  25. 25. Justifica resposta tão diferente entre os pacientes FUTURO EXOMA – DECISAO BASEADA NO PAINEL GENICO Gene do receptor androgênico (AR), localizado no cromossomo X, possui um segmento polimórfico da repetição CAG localizado no éxon 1. Indivíduos com resposta normal a ação dos hormônios androgênicos possuem de 11 a 31 repetições (alelos). • > 40 repetições estão relacionadas a uma diminuição da resposta androgênica.
  26. 26. Espermograma pré - medicação Fragmentação DNA sêmen – ISSM 2015 Atenção para sem prole ESPG Pré Finasterida - se ok - IFDNA - se alterado cessar ESPG com 6 meses (Espermatogênese – 87 dias ) TT pré – Se ≤ de 300 – reconsiderar Se IFDNA > 30% reconsiderar Sub férteis – Mandatória Descontinuação
  27. 27. Obrigado conradoalvarenga@gmail.com andrologia@labmedicinamasculina.com.br

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